Project Summary/ Abstract Despite the high prevalence of chronic pain and opioid use in hemodialysis patients, and compelling data associating chronic pain and opioid prescriptions with poor outcomes, evidence from clinical trials to address these problems in hemodialysis patients is lacking and signifies a pressing unmet clinical need. This proposal is to participate as a Clinical Center in the Hemodialysis Opioid Prescription Effort (HOPE) Consortium. Because pain is a multidimensional phenomenon with physical and psychosocial components, a unidimensional approach to pain management relying solely on analgesics is unlikely to be efficacious. Nonpharmacologic therapies for co-occurring chronic pain and opioid use in hemodialysis patients should target and alter cognitive-affective circuits that govern responses elicited by pain, stress, mood disorders, and opioid-related cues. These domains are directly addressed through the behavioral therapy program known as MORE (Mindfulness-Oriented Recovery Enhancement)?a multi-pronged mindfulness-oriented individualized group therapy that integrates mindfulness training, cognitive reappraisal, and enhancement of natural reward processing. The central hypothesis for this proposal is that MORE therapy will alter the dysfunctional cognitive, affective, and behavioral pathways that influence chronic pain perception and opioid use, resulting in significant reductions in pain severity and opioid use among hemodialysis patients, and that for patients with opioid use disorder, engagement in the MORE program will increase the likelihood of starting buprenorphine treatment. Guided by MORE's demonstrated efficacy in the general population, the specific aims are: 1) Determine the impact of MORE on chronic pain and opioid use in hemodialysis patients; and 2) Determine predictors of chronic pain, opioid use, and response to MORE. The approach to Aim 1 is an open-label, assessor-blinded, randomized superiority trial (1:1 randomization) comparing assignments to MORE therapy versus control conditions among adult hemodialysis patients with chronic pain treated with a ?90-day prescription of opioids (120 patients per Clinical Center). The Aim 2 approach will assess which comorbidities, psychological factors, and social determinants of health predict baseline pain and opioid dose (cross-sectional) as well as response to MORE (longitudinal) using data from patients enrolled in the clinical trial outlined in Aim 1. The proposed study will be critical to establish new avenues of research and clinical care that directly impact chronic pain management and opioid use in dialysis and general populations. The expected outcome is a comprehensive understanding of the impact of the MORE program on co-occurring chronic pain and opioid use in hemodialysis patients, and identification of future therapy targets. The proposed research is significant as it stands to improve quality of life, satisfaction, morbidity, and mortality in hemodialysis patients.